Cognitive impairment after surgery occurs frequently in the large number of increasingly elderly patients undergoing cardiac surgery (CS) every year. Postoperative cognitive decline (POCD) is present in 36-50% of patients in the early phases after surgery and has been shown to adversely impact quality of life as long as five years after surgery. Despite substantial advancement in technology, pharmacology, and perioperative organ protection leading to reductions in mortality associated with cardiac surgery, the incidence of POCD has changed little over the last ten years. Although perioperative cerebral edema as a consequence of ischemic white matter damage or emboli load has been identified as a contributing factor in POCD, gross ischemic damage or embolic showers are often not detected in CS patients and yet POCD complaints persist. Furthermore, the nature and relationship between functional network connectivity and POCD has never been examined in this patient population. The objective of our multidisciplinary Neurological Outcome Research Group is to understand the mechanisms underlying neurologic and neurocognitive dysfunction after cardiac surgery and to reduce the incidence of these devastating outcomes. As part of this long-term goal and on the basis of preliminary structural and functional neuroimaging data demonstrating regional post-CS differences in white matter patency and alterations in functionally connected brain networks, we now propose to study 55 subjects with an integrated imaging protocol and standardized cognitive testing battery. The primary aims of our prospective longitudinal study are to determine the frequency and nature of white matter patency and functional brain network changes associated with CS. We will also determine the relationship between white matter patency, functional network changes, cerebral embolism and measurable alterations in cognitive function after cardiac surgery. The results of our study will generate new mechanistic insights into the etiology and potential treatment of POCD. With the large number of patients undergoing CS, understanding the contributory nature and frequency of functional brain changes associated with POCD is an important step towards improving care and quality of life.